Ordóñez-Morán, P.Irmisch, A.Barbáchano, A.Chicote, I.Tenbaum, S.Landolfi, S.Tabernero, J.Huelsken, J.Muñoz, A.Pálmer, H. G.2014-05-192014-05-192014-05-19201410.1038/onc.2013.140https://infoscience.epfl.ch/handle/20.500.14299/103440WOS:000334346300010SPROUTY2 (SPRY2) is an intracellular regulator of receptor tyrosine kinase signaling involved in cell growth, differentiation and tumorigenesis. Here, we show that SPRY2 is a target gene of the Wnt/beta-catenin pathway that is abnormally activated in more than 90% of colon carcinomas. In human colon cancer cells, SPRY2 expression is induced by beta-catenin in co-operation with the transcription factor FOXO3a instead of lymphoid enhancer factor/T-cell factor proteins. We found binding of beta-catenin to the SPRY2 promoter at FOXO3a response elements. In vivo, cells marked by nuclear beta-catenin and FOXO3a express SPRY2 in proliferative epithelial tissues, such as intestinal mucosa and epidermis. Consistently, inducible beta-catenin deletion in mice reduced Spry2 expression in the small intestine. Moreover, SPRY2 protein expression correlated with nuclear beta-catenin and FOXO3a colocalization in human colon carcinomas. Importantly, the amount of SPRY2 protein correlated with shorter overall survival of colon cancer patients. Our data reveal SPRY2 as a novel Wnt beta-catenin and FOXO3a target gene indicative of poor prognosis in colon cancer.SPROUTY2wnt pathwaybeta-cateninFOXO3acolon cancertext::journal::journal article::research article